Masternak Michal M, Panici Jacob A, Bonkowski Michael S, Hughes Larry F, Bartke Andrzej
Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794, USA.
J Gerontol A Biol Sci Med Sci. 2009 May;64(5):516-21. doi: 10.1093/gerona/glp024. Epub 2009 Mar 20.
Reduced insulin sensitivity and glucose intolerance have been long suspected of having important involvement in aging. Here we report that in studies of calorie restriction (CR) effects in mutant (Prop1(df) and growth hormone receptor knockout [GHRKO]) and normal mice, insulin sensitivity was strongly associated with longevity. Of particular interest was enhancement of the already increased insulin sensitivity in CR df/df mice in which longevity was also further extended and the lack of changes in insulin sensitivity in calorically restricted GHRKO mice in which there was no further increase in average life span. We suggest that enhanced insulin sensitivity, in conjunction with reduced insulin levels, may represent an important (although almost certainly not exclusive) mechanism of increased longevity in hypopituitary, growth hormone (GH)-resistant, and calorie-restricted animals. We also report that the effects of GH treatment on insulin sensitivity may be limited to the period of GH administration.
长期以来，人们一直怀疑胰岛素敏感性降低和葡萄糖耐量异常与衰老密切相关。在此我们报告，在对突变体（Prop1(df)和生长激素受体基因敲除[GHRKO]）小鼠及正常小鼠进行的热量限制（CR）效应研究中，胰岛素敏感性与寿命密切相关。特别值得关注的是，CR df/df小鼠（其寿命也进一步延长）本已升高的胰岛素敏感性进一步增强，而热量限制的GHRKO小鼠（其平均寿命未进一步增加）的胰岛素敏感性未发生变化。我们认为，胰岛素敏感性增强与胰岛素水平降低相结合，可能是垂体功能减退、生长激素（GH）抵抗及热量限制动物寿命延长的一种重要（尽管几乎肯定不是唯一的）机制。我们还报告，GH治疗对胰岛素敏感性的影响可能仅限于GH给药期间。
